This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is focusing on developing and validating methods and techniques to demonstrate the applicability of AMS to assess human responses to drugs, xenobiotics and endogenous compounds. We are conducting studies using AMS to develop and validate methods for use in absorption, distribution, metabolism and elimination studies (ADME) using drugs alone and in combination. We will investigate how best to conduct basic metabolism studies as well as to work with isolated macromolecular fractions such as DNA modified by chemotherapy drugs. We will work in cell culture, animal models, and humans to assess what types of samples can be utilized and how best to process them for AMS analysis.